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Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis

ABSTRACT: Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis

PROVIDER: PRJNA771004 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16342700_1.fastq.gz	Fastqsanger.gz
	SRR16342700_2.fastq.gz	Fastqsanger.gz
	SRR16342800_1.fastq.gz	Fastqsanger.gz
	SRR16342800_2.fastq.gz	Fastqsanger.gz
	SRR16342701_1.fastq.gz	Fastqsanger.gz

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Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis [scRNA-Seq]

Project description:Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis [scRNA-Seq]

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Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis [RNA-Seq]

Project description:Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis [RNA-Seq]

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Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis [scRNA-Seq]

Project description:Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder, characterised by eruptions of painful, neutrophil-filled pustules on the palms and soles. While PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat. To investigate the immune pathways that underlie disease pathogenesis, we first undertook bulk RNA-sequencing in patient skin. We detected a pervasive and unexpected signature of T-cell activation, with a significant enrichment of Th2 pathways and evidence for a modest upregulation of Th17 genes. To further explore these findings, we carried out single-cell RNA-sequencing in peripheral blood mononuclear cells of healthy and affected individuals. We found that the memory CD4+T-cells of PPP patients were skewed towards a Th17 phenotype, a phenomenon that was particularly significant among CLA+ skin-homing cells. We also identified a subset of memory CD4+ T-cells which expressed both Th17 (KLRB1/CD161) and Th2 (GATA3) markers, with pseudo-time analysis suggesting that the population was the result of Th17 to Th2 plasticity. Interestingly, the GATA3+/CD161+ cells were over-represented among the PBMCs of affected individuals, both in the scRNA-seq dataset and in independent flow-cytometry experiments. Dual positive cells were also detected in patient skin by means of immune fluorescence microscopy. These observations demonstrate that PPP is associated with complex T-cell activation patterns and may explain why biologics that target individual T-helper populations have shown limited therapeutic efficacy.

2022-05-31 | GSE185857 | GEO

Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis [RNA-Seq]

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Based on Molecular Profiling of Gene Expression, Palmoplantar Pustulosis and Palmoplantar Pustular Psoriasis are Highly Related Diseases that Appear to Be Distinct from Psoriasis Vulgaris

2016-06-30 | GSE80047 | GEO

Th17 Cells with Regulatory Phenotype are the Main IL-17F and IL-26 Producers in Palmoplantar Pustulosis

Project description:Th17 Cells with Regulatory Phenotype are the Main IL-17F and IL-26 Producers in Palmoplantar Pustulosis

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Transcriptional profiling of Th1, Th2, Th9, and Th17 T cell clones

Project description:We next sought to identify the transcriptional program that differentiates IL-9+Th2 cells from “conventional” Th2 cells. To this end, we selected representative Th1, Th17, Th2, and IL-9+Th2 clones (Figure 5A) and determined their transcriptome in the resting state and at different time points after activation using RNAseq. Peripheral Blood Mononuclear Cells (PBMC) were isolated by Ficoll-Plaque Plus (GE Healthcare, UK) density gradient centrifugation. Human CD4+ T cells were isolated from PBMC by EasySep positive selection kit (Stemcell Technologies) according to manufacturer’s instruction. Positively selected CD4+ T cells were washed with PBS and stained for subsequent Th cell subset sorting. Memory Th cell subsets were sorted to over 90% purity according to their expression of chemokine receptors from CD45RA-CD25-CD8-CD3+ cells: Th1(CXCR3+CCR8-CCR6-CCR4-), Th2 (CXCR3-CCR8-CCR6-CCR4+), Th17 (CXCR3-CCR8-CCR6+CCR4+), Th9 (CXCR3-CCR8+CCR6-CCR4+). Single cell Th subset clones were directly sorted into 96well plate according to their expression of chemokine receptors (see above). Single cell clones were expanded and maintained by periodic restimulation with PHA (phytohaemaglutinine, 1 µg/ml, Sigma-Chemicals) and irradiated allogenic feeder cells (5x104/well) in culture medium. T cells were polyclonally activated using beads coated with antibodies against CD3, CD2, and CD28 (T cell/bead = 2:1, human T cell activation/expansion Kit, Miltenyi). Cell cultures were sampled before activation (time 0h) and 2, 4, 6, 9, 12, 24, and 48 hours after activation.

2017-11-10 | E-MTAB-5739 | biostudies-arrayexpress

Based on Molecular Profiling of Gene Expression, Palmoplantar Pustulosis and Palmoplantar Pustular Psoriasis are Highly Related Diseases that Appear to Be Distinct from Psoriasis Vulgaris

Project description:There is a controversy surrounding the existence of palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) as separate clinical entities or as variants of the same clinical entity. We used gene expression microarray to compare gene expression in PPP and PPPP. PPP and PPPP could not be differentiated using gene expression microarray suggesting that they are not distinct clinical entities. Increased expression of GPRIN1, and ADAM23 in keratinocytes suggests that these proteins could be new therapeutic targets for PPP/PPPP. Skin biopsies from subjects with PPP (3), PPPP (6), psoriasis vulgaris (10) and acral skin from normal subjects (7) were analyzed using gene expression microarray. Principal component analysis showed that PPP and PPPP were different from psoriasis vulgaris and normal acral skin. However gene expression of PPP and PPPP clustered together and could not be used to differentiate PPP from PPPP. Gene-wise comparison between PPP and PPPP found no gene to be differentially expressed with a false discovery rate lower than 0.6. Surprisingly we found a higher expression of several genes involved in neural pathways (e.g. GPRIN and ADAM23) in PPP/PPPP as compared to psoriasis vulgaris and normal acral skin. Immunohistochemistry confirmed those findings and showed a keratinocyte localization for those proteins.

2016-06-30 | E-GEOD-80047 | biostudies-arrayexpress

Th17 Cells with Regulatory Phenotype are the Main IL-17F and IL-26 Producers in Palmoplantar Pustulosis

Project description:Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder marked by erythematous pustules and desquamation on the palms and soles. While IL-17 pathways are implicated in PPP, IL-17 blockers have shown modest efficacy, underscoring the need for a deeper understanding of IL-17 involvement. To dissect the cellular and spatial architecture of PPP, we performed single-cell RNA sequencing (scRNA-seq) on lesional, nonlesional, and healthy acral skin to examine cellular composition, transcriptomic profiles, and cell-cell interactions. Unbiased clustering revealed nine major cell types, including an inflammatory keratinocyte subset enriched in IL-17A/TNF signatures and marked by high IL-36G expression. Within the lymphocyte compartment, we identified a hybrid “regTh17” population co-expressing regulatory markers (FOXP3, CTLA4, TIGIT), IL17F, and IL26. This regTh17 subset was distinguished by elevated IL1R1 and CD39, suggesting a IL-1β–driven differentiation. Spatial analyses demonstrated significant neighborhood enrichment of regTh17 cells with IL-36G⁺ supraspinous keratinocytes. RegTh17 cells were the predominant source of IL-17F and IL-26 signals, whereas keratinocytes were predicted as their main receivers. We further observed regTh17 co-expressing TNFRSF4 (OX40) and TNFRSF18 (GITR) specifically at sites of IL36G+ keratinocyte interactions, implicating these pathways in amplification of the IL-17/IL-36 inflammatory loop. Together, our integrated single-cell and spatial profiling uncovers Th17 plasticity in PPP, identifies a regTh17-keratinocyte interaction and highlights IL-17F, IL-26, OX40/OX40L, and GITR/GITRL as candidate targets for precision therapies in this challenging disease.

2025-08-06 | GSE304122 | GEO

Single-cell analysis implicates Th17 to Th2 cell plasticity in the pathogenesis of palmoplantar pustulosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-05-31 | GSE185858 | GEO